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miR-98 的上调抑制骨关节炎软骨细胞凋亡。

Upregulation of miR-98 Inhibits Apoptosis in Cartilage Cells in Osteoarthritis.

作者信息

Wang Gui-Long, Wu Yu-Bo, Liu Jia-Tian, Li Cui-Yun

机构信息

1 Department of Orthopedics, Linyi People's Hospital , Linyi, P.R. China .

2 Department of Pathology, Linyi People's Hospital , Linyi, P.R. China .

出版信息

Genet Test Mol Biomarkers. 2016 Nov;20(11):645-653. doi: 10.1089/gtmb.2016.0011. Epub 2016 Sep 27.

Abstract

OBJECTIVE

We aimed to investigate the effects of microRNA-98 (miR-98) on apoptosis in cartilage cells of osteoarthritis (OA) patients.

METHODS

Knee cartilage tissue samples were collected from 31 OA patients, 21 autopsies, and 26 amputation patients due to trauma. The clinicopathological data were recorded. Quantitative real-time polymerase chain reaction was performed to compare the miR-98 expression levels from cartilage cells obtained from the OA and non-OA patients. Clinicopathological characteristics of the patients were also analyzed. Primary chondrocytes were separated from cartilage tissues and transfected with plasmids or siRNA to overexpress or inhibit miR-98. Annexin V-PI double staining and TUNEL assays were used to examine apoptosis in the primary chondrocytes after transfection. Finally, a rat OA model was used to confirm the effects of miR-98 on apoptosis in cartilage cells in vivo.

RESULTS

Compared with the normal cartilage tissues, miR-98 expression was reduced in the OA cartilage tissues (p < 0.01). The miR-98 expression levels were also significantly correlated with the OA stage (p < 0.05). In vitro, transfection with the miR-98 inhibitor increased apoptosis in the cartilage cells (p < 0.05), and transfection with a miR-98 mimic inhibited apoptosis in cartilage cells (p < 0.05). In the OA rat model, exogenous injection of the miR-98 mimic inhibited apoptosis in the rat cartilage cells thus alleviating OA.

CONCLUSION

MiR-98 expression is reduced in the cartilage cells of OA patients and the overexpression of miR-98 inhibits cartilage cell apoptosis, while inhibition of microRNA-98 leads to cartilage cell apoptosis. These findings provide a theoretical basis for the development of novel targeted therapies for OA.

摘要

目的

我们旨在研究微小RNA - 98(miR - 98)对骨关节炎(OA)患者软骨细胞凋亡的影响。

方法

收集31例OA患者、21例尸检以及26例因创伤截肢患者的膝关节软骨组织样本。记录临床病理数据。采用定量实时聚合酶链反应比较OA患者和非OA患者软骨细胞中miR - 98的表达水平。还对患者的临床病理特征进行了分析。从软骨组织中分离出原代软骨细胞,用质粒或小干扰RNA转染以过表达或抑制miR - 98。转染后,采用膜联蛋白V - PI双染法和TUNEL检测法检测原代软骨细胞的凋亡情况。最后,使用大鼠OA模型在体内证实miR - 98对软骨细胞凋亡的影响。

结果

与正常软骨组织相比,OA软骨组织中miR - 98表达降低(p < 0.01)。miR - 98表达水平也与OA分期显著相关(p < 0.05)。在体外,用miR - 98抑制剂转染增加了软骨细胞凋亡(p < 0.05),而用miR - 98模拟物转染则抑制了软骨细胞凋亡(p < 0.05)。在OA大鼠模型中,外源性注射miR - 98模拟物抑制了大鼠软骨细胞凋亡,从而减轻了OA。

结论

OA患者软骨细胞中miR - 98表达降低;miR - 98过表达抑制软骨细胞凋亡,而抑制微小RNA - 98则导致软骨细胞凋亡。这些发现为开发针对OA的新型靶向治疗方法提供了理论依据。

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